Evidence mapPaperPMID 40938538Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

M2 Macrophages are Major Mediators of Germline Risk of Endometriosis and Explain Pleiotropy With Comorbid Traits.

Soledad Ochoa, Fernanda S Rasquel-Oliveira, Brett McKinnon, Marcela Haro, Sugarniya Subramaniam, Pak Yu, Simon Coetzee, Michael S Anglesio, Kelly N Wright, Raanan Meyer and 6 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Soledad OchoaDepartment of Obstetrics and Gynecology, University of Texas Health, San Antonio, TX, 78229, USA.ORCID https://orcid.org/0000-0003-2819-0486
Fernanda S Rasquel-OliveiraVascular Biology Program, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA, 02115, USA.
Brett McKinnonThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia, 4072.
Marcela HaroDepartment of Obstetrics and Gynecology, University of Texas Health, San Antonio, TX, 78229, USA.
Sugarniya SubramaniamThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia, 4072.
Pak YuWomen's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Simon CoetzeeCenter for Inherited Oncogenesis, University of Texas Health, San Antonio, TX, 78229, USA.
Michael S AnglesioBritish Columbia's Gynecological Cancer Research (OVCARE) Program, University of British Columbia, Vancouver General Hospital and BC Cancer, Vancouver, British Columbia, V6T 1Z1, Canada.
Kelly N WrightDivision of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Raanan MeyerDivision of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Anne E PorterDepartment of Obstetrics and Gynecology, University of Texas Health, San Antonio, TX, 78229, USA.
Caroline E GargettThe Ritchie Center, Hudson Institute for Medical Research, Melbourne, Victoria, 3168, Australia.
Sally MortlockThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia, 4072.
Grant W MontgomeryThe Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia, 4072.
Michael S RogersVascular Biology Program, Boston Children's Hospital, Department of Surgery, Harvard Medical School, Boston, MA, 02115, USA.
Kate LawrensonDepartment of Obstetrics and Gynecology, University of Texas Health, San Antonio, TX, 78229, USA.ORCID https://orcid.org/0000-0002-6469-2515

Funding

UCLA Clinical and Translational Science InstituteUL1TR001881 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$9.9M
Disentangling the genetic mechanisms of endometriosis severity with single-cell multi-omicsR01HD114855 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$699k
Functional Genomics Across an Ethnically and Racially Diverse Endometriosis PopulationR01HD113693 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$559k
Hormonal Influences on Inflammation in EndometriosisR01HG013258 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$466k
Cedars-Sinai Medical Center 134005Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD113693Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD114855Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HG013258National Health and Medical Research Council of Australia Investigator Grants GNT1173882National Health and Medical Research Council of Australia Investigator Grants GNT1177194NCATS NIH HHS UL1 TR001881NCATS NIH HHS UL1TR001881NHGRI NIH HHS R01 HG013258NICHD NIH HHS R01 HD113693NICHD NIH HHS R01 HD114855The Cedars-Sinai grant supportcThe JW and Alice Marriott FoundationThe Marriott Daughters foundationU.S. Department of Defense W81XWH1910364
6 · The paper itself

Abstract

Endometriosis is a common gynecologic condition that causes chronic, life-altering symptoms including pain and infertility. There is an urgent need for new non-hormonal targeted therapeutics to treat endometriosis, but until very recently, the cellular and molecular signatures of endometriotic lesions are undefined, hindering the development of clinical advances. Integrating inherited risk data from analyses of >45 0000 individuals with ≈35 0000 single-cell transcriptomes from 21 patients, M2-macrophages as candidate drivers of disease susceptibility are uncovered, and nominating IL1 signaling as a central hub impacted by germline genetic variation associated with endometriosis risk. Extensive functional follow-up confirmed these associations and revealed a pleiotropic role for this pathway in endometriosis. Population-scale expression quantitative trait locus analysis demonstrates that genetic variation controlling IL1A expression is associated with endometriosis risk variants. Manipulation of IL1 signaling in state-of-the-art in vitro decidualized endometrial organoids impacts epithelial differentiation, and in an in vivo endometriosis model, treatment with anakinra (an interleukin-1 receptor antagonist) results in a significant, dose-dependent reduction in spontaneous and evoked pain and dampened pro-angiogenic signaling. Together, these studies highlight non-diagnostic cell types as central to endometriosis susceptibility and support IL1 signaling as an important actionable pathway for this disease.

Indexed as

EndometriosisMacrophagesAnimalsComorbidityFemaleGenetic Predisposition to DiseaseHumansInterleukin 1 Receptor Antagonist ProteinInterleukin 1 Receptor Antagonist ProteinanakinraangiogenesisendometriosisGWASIL1AIL1BinflammationM2 macrophagesorganoidssingle cell transcriptomics

Identifiers

PMID40938538
PMCPMC12591210

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.